The standard therapy for cancer is radio- or chemotherapy. However, these are by no means effective for everyone and have numerous undesirable and stressful side effects. The reason: they attack not only the diseased cells but the entire organism. It also increases the risk of becoming resistant to therapy.
Scientists at the University of Geneva (UNIGE, Switzerland) have now developed a technique that is not only more effective than chemotherapy but also has no adverse side effects. This therapy enables the optimal combination and dosage of substances that can kill tumor cells while not adversely affecting healthy cells. These can also now be found quickly amongst a wide range of existing drugs. Researchers have already been able to demonstrate the effectiveness of this method in colon cancer. They did this in collaboration with the University Hospital of Geneva (HUG) and the University Hospital of Amsterdam (the Netherlands).
In vitro and in vivo
In order to be able to evaluate the best drug combinations, the scientists first used in vitro tests and, for the first time ever, in vivo tests in mouse models. All combinations proved to be more effective than chemotherapy. Nor did they cause any apparent toxicity in either healthy cells or animals, the researchers stated.
“The technique we have developed and patented is called TGMO, which stands for phenotypically controlled, therapy-guided multidrug optimization. It combines tests and advanced statistical analysis,” says Patrycja Nowak-Sliwinska, Professor at the Faculty of Pharmaceutical Sciences of the UNIGE’s Faculty of Science. “It allows us to perform tests on cancerous and healthy cells (from the same patient) at the same time in just a few steps. And to evaluate all potential drug combinations that we have selected for this purpose. The positive synergies are maintained while the antagonisms are rejected.”
The experiment was carried out with 12 drugs. All of these had been recently approved for commercialization, or are in the final stages of clinical trials. “Colon cancer cell strains that had been perfectly characterized for the requirements of the scientific studies were submitted to the TGMO-based ‘machinery’,” the researchers went on to explain. “The aim of the search was to identify the product combinations that came closest to the desired result. As in, the demise of the cancerous cell with the simultaneous absence of effect on the healthy cell. And all this at the lowest possible dosage of the drugs.” This procedure led to multiple combinations of three or four drugs, all slightly different from each other.
Tumor growth reduced by 80%
In the next step, the combinations were tested on a three-dimensional model of a human tumor. Then they used mice as an experimental model for colon cancer. The results indicated that the drug combinations that were tested reduced tumor growth by about 80%. This means they were thus significantly more effective than chemotherapy. The healthy cells were not affected. The research was limited to cancer cells that were “freshly taken from actual patients in Switzerland.”
“This is the first time that in vivo tests have been undertaken with drug combinations derived from our TGMO technology,” Patrycja Nowak-Sliwinska enthuses. “The study shows that it is possible to discover low-dose, synergistic, and selectively optimized drug combinations that are more effective than conventional chemotherapy, regardless of the mutation status of the tumor and in an efficient way.” A clinical trial in patients is currently under discussion “so that we can go one step further. But this is principally the work of clinical doctors. Plus the funding of this stage depends very much on the interest that a private sector might have in our approach.”
Results in less than two weeks
Results in less than two weeks
The TGMO technology is designed to deliver results in under two weeks, the researchers claim. This is the same amount of time that doctors need after diagnosis for determining a therapy. “This approach clearly represents the future for oncology patients,” says Thibaud Koessler. He is head of Gastrointestinal Oncology in the Department of HUG Oncology. And he is one of the authors of the article published in the journal Molecular Oncology. “The option of testing different drugs ex vivo and selecting for each patient the combination that the cancer is most sensitive to should increase the effectiveness of therapies while reducing toxicity. These are two of the most problematic aspects of the current therapies.”
Title picture: Schematic diagram of colon and colorectal cancer. © UNIGE/Nowak-Sliwinska